Over the past 18 months laser tissue interaction studies using Excimer lasers (both Xenon Chloride-308nm and Krypton Fluoride-248nm) have been performed to define specific ablative thresholds and ablative efficiency, as well as the mechanisms of tissue ablation for human normal and atherosclerotic specimens. However, before clinical trials can be considered, the efficiency of transmitting fibers and efficacy of Excimer laser angioplasty in animal models must be carefully determined. Thus, a XeCl Excimer laser (40 nsec pulses) was delivered through commercial 600u silicon fibers in saline and whole blood wet fields. The ablative threshold and efficiency was similar to previous experiments without fibers in air using both normal sheep aorta and human necropsy specimens. The depth of ablation was linearly related to energy density and fiber damage occurred at fluences 5-6 times greater than the ablative threshold. Thus, a narrow operating margin between ablative threshold and fiber damage was defined mandating fiber-target contact to ensure predictable tissue ablation. Thereafter, Excimer laser angioplasty was attempted in New Zealand white rabbits which were fed a 2% cholesterol diet followed by endothelial balloon barotrauma to induce focal severe atherosclerosis in the iliofemoral arterial system bilaterally. Attempted recanalization of stenosed or occluded iliac arteries resulted in angiographic perforations in every animal. The histology of excised vessels was without significant thermal injury and perforations were due largely to fiber stiffness and mechanical factors. Therefore, we have concluded that XeCl Excimer lasers can be transmitted by fibers at energy densities sufficient to cause precise tissue ablation without significant thermal tissue injury, but Excimer laser angioplasty in an atherosclerotic rabbit model was associated with frequent vascular perforations emphasizing the need for more flexible delivery systems.